Hemophilia A is an inherited bleeding disorder that stems from lack of coagulation factor VIII (F.VIII). Crude preparations of plasma-derived F.VIII used in treatment of hemophilia are in short supply worldwide and F.VIII can be prepared using immunoaffinity column chromatography, conventional affinity separations technology is poorly suited to large scale production of purified F.VIII. The objective of the proposed research is to develop a membrane-based affinity process for purification of F.VIII directly from blood plasma. In contrast to conventional technologies, we expect that membrane affinity processes will offer high specificity and yield, and yet be amenable to industrial operations. In the Phase I research, the technical feasibility of membrane immunoaffinity purification of F.VIII from plasma was established. In Phase II, the F.VIII purification process will be optimized and scaled up for production of materials for preclinical studies. F.VIII thus purified will be extensively characterized and tested for safety in animals. The purpose of this project is to establish the technical basis for membrane-mediated affinity purification of F.VIII, to develop a general approach to industrial affinity separations, and to improve the quality of life of individuals currently undergoing factor VIII replacement therapy.